Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Wonuola A Akingbuwa, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute
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  • Anke R Hammerschlag, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, The University of Queensland
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  • Eshim S Jami, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute
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  • Andrea G Allegrini, King’s College London
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  • Ville Karhunen, Imperial Coll London, Imperial College London, Imperial Clin Trials Unit
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  • Hannah Sallis, University of Bristol School of Psychological Science, University of Bristol
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  • Helga Ask, Norwegian Institute of Public Health
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  • Ragna B Askeland, Norwegian Institute of Public Health
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  • Bart Baselmans, Vrije Universiteit Amsterdam
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  • Elizabeth Diemer, Erasmus University Medical Center
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  • Fiona A Hagenbeek, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute
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  • Alexandra Havdahl, University of Bristol, Lovisenberg Diaconal Hospital, Norwegian Institute of Public Health
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  • Jouke-Jan Hottenga, Vrije Universiteit Amsterdam
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  • Hamdi Mbarek, Vrije Universiteit Amsterdam, Qatar Foundation
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  • Fernando Rivadeneira, University Medical Center Rotterdam
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  • Martin Tesli, Norwegian Institute of Public Health
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  • Catharina van Beijsterveldt, Vrije Universiteit Amsterdam
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  • Gerome Breen, King’s College London, South London and Maudsley National Health Services Foundation Trust
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  • Cathryn M Lewis, King’s College London
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  • Anita Thapar, Cardiff Univ, Cardiff University, Cardiff Business Sch
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  • Dorret I Boomsma, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute
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  • Ralf Kuja-Halkola, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital
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  • Ted Reichborn-Kjennerud, Norwegian Institute of Public Health, University of Oslo
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  • Per Magnus, Norwegian Institute of Public Health
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  • Kaili Rimfeld, King’s College London
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  • Eivind Ystrom, Norwegian Institute of Public Health, University of Oslo
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  • Marjo-Riitta Jarvelin, Imperial Coll London, Imperial College London, Imperial Clin Trials Unit, University of Oulu, Medical Research Center Oulu, Brunel University London
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  • Paul Lichtenstein, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital
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  • Sebastian Lundstrom, Univ Gothenburg, University of Gothenburg, Gothenburg Global Biodivers Ctr
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  • Marcus R Munafò, University of Bristol School of Psychological Science, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
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  • Robert Plomin, King’s College London
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  • Henning Tiemeier, Erasmus University Medical Center, Harvard T. H. Chan School of Medicine
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  • Michel G Nivard, Vrije Universiteit Amsterdam
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  • Meike Bartels, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute
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  • Christel M Middeldorp, Vrije Universiteit Amsterdam, The University of Queensland, Children’s Health Queensland Hospital and Health Service
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  • and the Bipolar Disorder and Major Depressive Disorder Working Groups of the Psychiatric Genomics Consortium

Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits.

Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders.

Design, Setting, and Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019.

Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI).

Main Outcomes and Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater.

Results: The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, -0.0001 [Δ95% CI, -0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, -0.0310 [Δ95% CI, -0.0456 to -0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, -0.0032 [Δ 95% CI, -0.0048 to -0.0017]; ΔSE, 0.0008).

Conclusions and Relevance: Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.

Original languageEnglish
JournalJAMA Psychiatry
Volume77
Issue7
Pages (from-to)715-728
Number of pages14
ISSN0003-990X
DOIs
Publication statusPublished - Jul 2020

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